自拟安神方对心肾不交证失眠大鼠的作用研究  

Effect of Self-prepared Anshen Recipe on Insomnia Rats with Incoordination between Heart and Kidney Syndrome

作　　者：李雪 徐雅 杜庆红 白俊杰[2,3] 王旭 李靖 LI Xue;XU Ya;DU Qinghong;BAI Junjie;WANG Xu;LI Jing(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102401,China;Beijing University of Chinese Medicine,Beijing 100029,China;University of Tibetan Medicine,Lhasa 850000,China)

机构地区：[1]北京中医药大学中医学院,北京102401 [2]北京中医药大学,北京100029 [3]西藏藏医药大学,拉萨850000

出　　处：《中国中医基础医学杂志》2022年第11期1806-1811,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：西藏自治区藏医药管理局级科技专项(JJKT2020006)-基于网络药理学探索“西红花-牛黄”配伍抗肝纤维化的机制;西藏自治区科技计划重点研发计划项目(XZ202201ZY0019G)-基于肝纤维化的藏药七味铁屑胶囊二次开发-临床前药效评价与机制探索;西藏自治区教育厅项目(90020171720022)-基于《四部医典》基础理论的藏中药结合用于新型冠状病毒肺炎恢复期治疗的基本方剂研究。

摘　　要：目的 从下丘脑-垂体-肾上腺轴(hypothalamic pituitary adrenal axis, HPA)功能及神经递质含量变化探讨自拟安神方(简称安神方)对心肾不交证失眠大鼠的作用。方法 复合因素刺激及腹腔注射DL-4-氯苯基丙氨酸(para-chlorophenylalanine, PCPA)制备心肾不交证失眠大鼠模型,造模成功后随机分为模型组,安神方高、中、低剂量组及阳性对照组,另设正常组每组各10只,分别灌胃相应药物2周。戊巴比妥钠翻正实验观察造模情况,旷场实验观察大鼠的紧张和焦虑情绪,Elisa法检测大鼠血清促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)、促肾上腺皮质激素释放激素(corticotropin-releasing hormone, CRH)、皮质醇(cortisol, CORT)的含量,高效液相色谱-电化学法检测大鼠下丘脑中多巴胺(dopamine, DA)和5-羟色胺(5-hydroxytryptamine, 5-HT)的含量。结果 造模后模型组大鼠体质量下降(P<0.05),睡眠潜伏期延长(P<0.01),睡眠持续时间显著减少(P<0.01),说明心肾不交证失眠模型复制成功。给药后安神方3剂量组大鼠2周体质量增量升高(P<0.05),直立次数减少(P<0.05),睡眠持续时间均显著延长(P<0.01),CRH含量降低(P<0.05),安神方低、中剂量组总活动距离减少(P<0.05);安神方中、高剂量组大鼠睡眠潜伏期均显著缩短(P<0.01),DA含量均降低(P<0.05);安神方低剂量组5-HT含量升高(P<0.05)。结论 自拟安神方能显著改善心肾不交证大鼠的失眠症状,推测其机制可能与抑制HPA轴兴奋、降低下丘脑DA的含量、同时升高5-HT的含量有关。Objective: To observe the effect and mechanism of Self-prepared Anshen Recipe(ASF) on insomnia rats with incoordination between heart and kidney syndrome from the function of hypothalamic pituitary adrenal axis(HPA) and the changes of neurotransmitter. Methods: Multifactorial stimulus and intraperitoneal injection of PCPA were used to make rat model of insomnia. After successful modeling, rats were randomly divided into model group, positive control group, high-dose, medium-dose and low-dose groups of ASF and normal group. Ten rats in each groups were given different drugs for 2 weeks. The sleep latency and sleep duration of rats were observed by pentobarbital sodium inversion test. The stress and anxiety of rats were observed by open field test.CRH, ACTH and CORT in serum of HPA were detected by Elisa. The content of neurotransmitters in rat hypothalamus were detected by high performance liquid chromatography-electrochemical method. Results: After modeling, the increase of body weight in model group was significantly reduced(P<0.05), the sleep latency time was obviously longer(P<0.01), the sleep duration was obviously shortened(P<0.01), indicating that the model of insomnia with incoordination between heart and kidney syndrome was successfully replicated. After administration, the body weight gain of ASF groups in 2 weeks was higher(P<0.05),the content of CRH and the upright times of ASF groups were decreased(P<0.05),the sleep duration was significantly prolonged in ASF groups(P<0.01).The total active distance of low-dose and medium-dose of ASF were decreased(P<0.05),the sleep latency of high-dose and medium-dose of ASF groups were shortened(P<0.01), the content of DA was decreased(P<0.05).The content of 5-HT of low-dose of ASF group was increased(P<0.05). Conclusion: ASF can significantly improve the symptoms of insomnia in rats with incoordination between heart and kidney syndrome, which may be related with the inhibition of HPA axis, the decrease of DA content and the increase of 5-HT content in hypothalamus.

关 键 词：自拟安神方 心肾不交证 失眠 HPA轴 DA 5-HT 

分 类 号：R338.63[医药卫生—人体生理学]